ZNF70, a novel ILDR2-interacting protein, contributes to the regulation of HES1 gene expression

Biochem Biophys Res Commun. 2016 Sep 2;477(4):712-716. doi: 10.1016/j.bbrc.2016.06.124. Epub 2016 Jun 25.

Abstract

A diabetes susceptibility gene, immunoglobulin-like domain containing receptor 2 (Ildr2), encodes a transmembrane protein localized to the endoplasmic reticulum membrane that is closely related to hepatic lipid metabolism. The livers of ob/ob mice in which Ildr2 is transiently overexpressed are relieved of hepatic steatosis. However, the molecular mechanisms through which ILDR2 affects these changes in hepatic lipid metabolism remain unknown. This study aimed to identify ILDR2-interacting proteins to further elucidate the molecular mechanisms underlying the role of ILDR2 in lipid homeostasis. We purified ILDR2-containing protein complexes using tandem affinity purification tagging and identified ZNF70, a member of the Kruppel C2H2-type zinc finger protein family, as a novel ILDR2-interacting protein. We demonstrated that ZNF70 interacts with ZFP64 and activates HES1 transcription by binding to the HES1 promoter. In addition, HES1 gene expression is increased in ILDR2-knockdown HepG2 cells, in which ZNF70 is translocated from the cytoplasm to the nucleus, suggesting that ZNF70 migration to the nucleus after dissociating from the ILDR2-ZNF70 complex activates HES1 transcription. These results support a novel link between ILDR2 and HES1 gene expression and suggest that ILDR2 is involved in a novel pathway in hepatic steatosis.

Keywords: HES1 gene expression; ILDR2-Interacting protein; Kruppel C2H2-type zinc-finger protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cell Nucleus / metabolism*
  • Gene Expression Regulation / physiology*
  • HEK293 Cells
  • Hep G2 Cells
  • Humans
  • Membrane Proteins / metabolism*
  • Protein Binding
  • Protein Transport / physiology*
  • Signal Transduction / physiology
  • Transcription Factor HES-1 / chemistry
  • Transcription Factor HES-1 / metabolism*
  • Zinc Fingers / physiology*

Substances

  • ILDR2 protein, mouse
  • Membrane Proteins
  • Transcription Factor HES-1
  • HES1 protein, human